Recent advances in sarcoidosis genomics: epigenetics, gene expression, and gene by environment (G × E) interaction studies

Curr Opin Pulm Med. 2020 Sep;26(5):544-553. doi: 10.1097/MCP.0000000000000719.


Purpose of review: We aim to review the most recent findings in genomics of sarcoidosis and highlight the gaps in the field.

Recent findings: Original explorations of sarcoidosis subphenotypes, including cases associated with the World Trade Center and ocular sarcoidosis, have identified novel risk loci. Innovative gene--environment interaction studies utilizing modern analytical techniques have discovered risk loci associated with smoking and insecticide exposure. The application of whole-exome sequencing has identified genetic variants associated with persistent sarcoidosis and rare functional variations. A single epigenomics study has provided background knowledge of DNA methylation mechanisms in comparison with gene expression data. The application of machine-learning techniques has suggested new drug repositioning for the treatment of sarcoidosis. Several gene expression studies have identified prominent inflammatory pathways enriched in the affected tissue.

Summary: Certainly, sarcoidosis research has recently advanced in the exploration of disease subphenotypes, utilizing novel analytical techniques, and including measures of clinical variation. Nevertheless, large-scale and diverse cohorts investigated with advanced sequencing methods, such as whole-genome and single-cell RNA sequencing, epigenomics, and meta-analysis coupled with cutting-edge analytic approaches, when employed, will broaden and translate genomics findings into clinical applications, and ultimately open venues for personalized medicine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Epigenesis, Genetic*
  • Epigenomics
  • Gene Expression*
  • Gene-Environment Interaction*
  • Genome-Wide Association Study
  • Genomics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Precision Medicine
  • Sarcoidosis / epidemiology
  • Sarcoidosis / genetics*
  • Sequence Analysis, RNA
  • Single-Cell Analysis
  • Whole Exome Sequencing